Publications by authors named "Yann Alexandre Vano"

Background: Immunotherapies targeting PD-1 and CTLA-4 are key components of the treatment of metastatic clear cell renal cell carcinoma (mccRCC). However, they have distinct safety profiles and resistance to treatment can occur. We assess soluble TIM-3 (sTIM-3) in the plasma of mccRCC patients as a potential theranostic biomarker, as well as its source and biological significance.

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Background: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. While the dysregulation of ERV transcription has been linked to immune cell infiltration in various cancers, its relationship with immune checkpoint inhibitor (ICI) response in solid tumors, particularly metastatic clear-cell renal cell carcinoma (ccRCC), remains inadequately explored.

Methods: This study analyzed patients with metastatic ccRCC from two prospective clinical trials, encompassing 181 patients receiving nivolumab in the CheckMate trials (-009 to -010 and -025) and 48 patients treated with the ipilimumab-nivolumab combination in the BIONIKK trial.

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Evolution of the support kidney cancer: place of biomarkers and prognostic factors.

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Article Synopsis
  • The study examines how individual differences in drug absorption (pharmacokinetics) impact the effectiveness and side effects of cabozantinib in patients with metastatic renal cell carcinoma (mRCC).
  • Out of 78 patients analyzed, 67% experienced dose-limiting toxicity, and higher drug concentration in the blood was identified as a significant risk factor for these side effects.
  • The research suggests that monitoring drug levels early in treatment could help optimize cabozantinib therapy, particularly for frail patients starting on lower doses.
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The efficacy of immune checkpoint inhibitors varies in clear-cell renal cell carcinoma (ccRCC), with notable primary resistance among patients. Here, we integrate epigenetic (DNA methylation) and transcriptome data to identify a ccRCC subtype characterized by cancer-specific promoter hypermethylation and epigenetic silencing of Polycomb targets. We develop and validate an index of methylation-based epigenetic silencing (iMES) that predicts primary resistance to immune checkpoint inhibition (ICI) in the BIONIKK trial.

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Importance: Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti-programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor.

Objective: To assess the antitumor activity and safety of dostarlimab in patients with advanced or recurrent dMMR solid tumors.

Design, Setting, And Participants: The GARNET trial was a phase 1, open-label, single-group, multicenter study that began enrolling May 8, 2017.

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Collecting duct carcinoma (also known as Bellini tumour) and renal medullary carcinoma are two extremely rare and aggressive renal cancers. They are both less responsive to conventional treatments used in clear cell renal carcinoma. There are very few studies evaluating their optimal management and currently, at the metastatic stage, polychemotherapy based on platinum salts remains the most widely used.

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Background: There remains a paucity of data regarding the efficacy of immune checkpoint therapy (ICT) combinations ± vascular endothelial growth factor (VEGF) targeted therapy (TT) in translocation renal cell carcinoma (tRCC).

Methods: This is a retrospective study of patients with advanced tRCC treated with ICT combinations at 11 centers in the US, France, and Belgium. Only cases with confirmed fluorescence in situ hybridization (FISH) were included.

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MiTF/TFE translocation renal cell carcinoma (tRCC) is a rare and aggressive subtype of RCC representing the most prevalent RCC in the pediatric population (up to 40%) and making up 4% of all RCCs in adults. It is characterized by translocations involving either TFE3 (TFE3-tRCC), TFEB (TFEB-tRCC) or MITF, all members of the MIT family (microphthalmia-associated transcriptional factor). TFE3-tRCC was first recognized in the World Health Organization (WHO) classification of kidney cancers in 2004.

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The field of clear cell renal cell carcinoma (ccRCC) has undergone major changes in the last decade, both in terms of the understanding of the mechanisms of oncogenesis and the role of the tumor microenvironment in anti-tumor immunity, as well as in therapeutic developments. After the era of tyrosine kinase inhibitors (TKIs) targeting VEGFR and then the era of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway, we are now entering the era of combination therapy for first-line metastatic cancer (m-ccRCC), such as combinations including a TKI and a PD-1 inhibitor or combinations of PD-1 and CTLA-4 blockers. In this extremely dynamic environment, new molecules with various mechanisms of action will appear in the very near future: immune response modulators (other ICIs, pro-inflammatory cytokines, gut microbiota modulators), new anti-angiogenic agents (new TKIs, anti-HIF-1α antibodies), agents affecting cell metabolism (glutaminase inhibitors, tryptophan regulators or adenosine A2A receptor antagonists) or epigenetic regulators (HDAC inhibitors).

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Nivolumab and cabozantinib are approved agents in mRCC patients after sunitinib/pazopanib (TKI) failure. However, the optimal sequence, cabozantinib then nivolumab (CN) or nivolumab then cabozantinib (NC), is still unknown. The CABIR study aimed to identify the optimal sequence between CN and NC after frontline VEGFR-TKI.

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Article Synopsis
  • Researchers conducted a phase 2 trial to evaluate the effectiveness and safety of nivolumab, nivolumab-ipilimumab, and VEGFR-TKIs in patients with metastatic clear-cell renal cell carcinoma based on their tumor's molecular characteristics.
  • The study included eligible patients from 15 healthcare centers in France, assigning them to different treatment groups through a randomized approach.
  • The primary goal was to assess how well these treatments worked, measured by the objective response rate, with safety also being monitored among patients receiving at least one dose of the medication.
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Article Synopsis
  • - The CheckMate 214 trial showed that combining nivolumab and ipilimumab is more effective than sunitinib as a first-line treatment for advanced clear-cell renal cell carcinoma (RCC), but there’s a need to figure out which patients will benefit most from this combo treatment.
  • - Researchers explored various biomarkers, including proteins and genetic signatures, but found that those previously linked to other treatments did not predict survival outcomes for patients using nivolumab plus ipilimumab.
  • - The study identified a link between tumor inflammation and better progression-free survival, suggesting that understanding the tumor's inflammatory environment could lead to improved strategies for personalized treatment in RCC patients.
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The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation.

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Introduction: Immune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors.

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Article Synopsis
  • The introduction of antiangiogenic treatments and immune checkpoint inhibitors has transformed how metastatic clear cell renal cell cancer is treated, particularly through combination therapies that outperform sunitinib alone.
  • Phase III trials favor combinations like pembrolizumab + axitinib, cabozantinib + nivolumab, and lenvatinib + pembrolizumab as first-line treatments, along with nivolumab + ipilimumab for higher-risk patients.
  • Ongoing challenges include determining the optimal combination for individual patients, assessing PD-L1 status, and addressing strategies for second-line therapies.
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The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings.

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Cabazitaxel (25 mg/m every 3 weeks) is the standard second-line chemotherapy for patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. It is associated with a risk of neutropenic complications, which may be a barrier to its use in daily clinical practice, particularly in frail elderly patients. Here the authors reviewed key studies conducted with cabazitaxel (TROPIC, PROSELICA, AFFINITY, CARD and the European compassionate use program) and pilot studies with adapted schedules.

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Renal cell carcinoma (RCC) is the seventh most frequently diagnosed malignancy with an increasing incidence in developed countries. Despite a greater understanding of the cancer biology, which has led to an increase of therapeutic options, metastatic clear cell renal cell carcinoma (mccRCC) still have a poor prognosis with a median five-years survival rate lower than 10%. The standard of care for mccRCC has changed dramatically over the past decades with the emergence of new treatments: anti-VEGFR tyrosine kinase inhibitors, mTOR Inhibitors and immune checkpoint inhibitors (ICI) such as anti-Programmed cell-Death 1 (PD-1) and anti-anti-Programmed Death Ligand-1 (PD-L1) used as monotherapy or as a combination with anti CTLA-4 or anti angiogenic therapies.

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In the last few years, the standard of care for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically with the emergence of the immune checkpoint inhibitors (ICI): anti-PD(L)-1 used as a monotherapy or as in combination either with an anti CTLA-4 or with an anti-angiogenic molecule (VEGFR tyrosine kinase inhibitor (TKI)). These combinations are now recommended in first line setting for mccRCC, according to the last European recommendations. In the face of these new therapeutic options, the question of selecting the best treatment arises as well as the optimal sequence.

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Background: Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in localized muscle-invasive bladder cancer (MIBC). However, 60-70% of patients have residual tumor after NAC. Based on the overall response rate observed in the metastatic setting, ddMVAC is the most commonly used NAC regimen in Europe.

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Background: The nivolumab-ipilimumab combination provides an overall response rate of 42% in first-line metastatic treatment of clear cell renal carcinoma (mccRCC). To date, there is no robust predictive biomarker of response to immune checkpoint inhibitor (ICI). In addition, severe autoimmune disorders occur more frequently with ICI combination than with ICI alone.

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